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Review
. 2021 Jan 7;9(1):26.
doi: 10.3390/vaccines9010026.

The Next Generation of Influenza Vaccines: Towards a Universal Solution

Christopher L D McMillan  1 , Paul R Young  1   2   3 , Daniel Watterson  1   3 , Keith J Chappell  1   2   3
Affiliations
Review

The Next Generation of Influenza Vaccines: Towards a Universal Solution

Christopher L D McMillan et al. Vaccines (Basel). .

Abstract

Influenza viruses remain a constant burden in humans, causing millions of infections and hundreds of thousands of deaths each year. Current influenza virus vaccine modalities primarily induce antibodies directed towards the highly variable head domain of the hemagglutinin protein on the virus surface. Such antibodies are often strain-specific, meaning limited cross-protection against divergent influenza viruses is induced, resulting in poor vaccine efficacy. To attempt to counteract this, yearly influenza vaccination with updated formulations containing antigens from more recently circulating viruses is required. This is an expensive and time-consuming exercise, and the constant arms race between host immunity and virus evolution presents an ongoing challenge for effective vaccine development. Furthermore, there exists the constant pandemic threat of highly pathogenic avian influenza viruses with high fatality rates (~30-50%) or the emergence of new, pathogenic reassortants. Current vaccines would likely offer little to no protection from such viruses in the event of an epidemic or pandemic. This highlights the urgent need for improved influenza virus vaccines capable of providing long-lasting, robust protection from both seasonal influenza virus infections as well as potential pandemic threats. In this narrative review, we examine the next generation of influenza virus vaccines for human use and the steps being taken to achieve universal protection.

Keywords: hemagglutinin; influenza; pandemic; universal influenza vaccine; vaccine.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Phylogeny and structure of influenza virus hemagglutinin. (a) A rooted phylogenetic tree based on the amino acid sequences of hemagglutinin (HA) sequences from influenza A and B viruses, adapted from Noh et al. [12]. (b) The structure of the ectodomain of the influenza hemagglutinin protein from the A/California/04/2009(H1N1) virus (PDB ID 3LZG). One HA monomer is shown with the HA1 subunit in red and the HA2 subunit in blue.
Figure 2
Figure 2
A schematic outlining chimeric HA-based vaccination approaches. A subject is immunized with a chimeric HA with an exotic head domain but a stem domain for the target virus. Following from this, a second vaccination can be administered with a chimeric HA with a consistent stem domain but another, different, exotic head domain. This can continue in order to selectively boost antibody responses towards the conserved stem domain while not boosting head-specific antibodies.
Figure 3
Figure 3
The structure of antibody CD6 in complex with influenza A virus neuraminidase (NA). (a) Top view of the NA–antibody complex. (b) Side view of the NA–antibody complex. Data retrieved from the Protein Data Bank (PDB ID 4QNP).
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